Sodium borohydride → N,N-Dibutyl-4-chloro-1-(2-((R)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(naphthalen-2-ylsulfonylcarbamoyl)phenyl)-5-methyl-1H-pyrazole-3-carboxamide

Participants

Reaction Steps

To a solution of (3R)-methyl 2-(2-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (Intermediate 85, 40 mg, 0.050 mmol) in THF (835 μL) and MeOH (170 μL) was added NaBH4 (4 mg, 0.10 mmol). The resulting reaction mixture was stirred at room temperature for 1 h. Additional NaBH4 (20 mg, 0.50 mmol) was added and stirring was continued at room temperature for 30 min. The reaction mixture was then quenched with water, poured into sat. aq. NH4Cl solution and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered, concentrated in vacuo and purified by preparative HPLC to give the title compound (13 mg, 34%). 1H NMR (1:1 CD3OD:CDCl3, mixture of amide rotamers) δ 8.68-8.77 (m, 1H), 8.23 (s, 0.5H), 8.13-7.99 (m, 4.5H), 7.95 (d, J=7.0 Hz, 1.5H), 7.72-7.61 (m, 1H), 7.58-7.45 (m, 1H), 7.23-7.03 (m, 4H), 6.87 (br s, 0.5H), 5.24 (d, J=18.0 Hz, 0.5H), 4.87 (br s, 0.5H), 4.49 (br s, 0.5H), 4.28 (d, J=17.4 Hz, 1H), 4.12 (br s, 1H), 3.63-3.52 (m, 1H), 3.51-3.34 (m, 1.5H), 3.27-2.92 (m, 4H), 2.83-2.53 (m, 1H), 2.28-2.25 (m, 3H), 1.62-0.83 (m, 11H), 0.77-0.69 (m, 2H), 0.64 (br s, 1H); MS(ESI+) m/z 770.3 (M+H)+.

Provenance & Evidence